Association of mutations in FLNA with craniosynostosis

作者：Fennell Nathalie; Foulds Nicola; Johnson Diana S; Wilson Louise C; Wyatt Michelle; Robertson Stephen P; Johnson David; Wall Steven A; Wilkie Andrew O M^*

来源：European Journal of Human Genetics, 2015, 23(12): 1684-1688.

DOI：10.1038/ejhg.2015.31

Mutations of FLNA, an X-linked gene that encodes the cytoskeletal protein filamin A, cause diverse and distinct phenotypes including periventricular nodular heterotopia and otopalatodigital spectrum disorders (OPDS). Craniofacial abnormalities associated with OPDS include supraorbital hyperostosis, down-slanting palpebral fissures and micrognathia; craniosynostosis was previously described in association with FLNA mutations in two individual case reports. Here we present four further OPDS subjects who have pathological FLNA variants and craniosynostosis, supporting a causal link. Together with the previously reported patients, frontometaphyseal dysplasia was the most common clinical diagnosis (four of six cases overall); five patients had multiple suture synostosis with the sagittal suture being the most frequently involved (also five patients). No genotypephenotype correlation was evident in the distribution of FLNA mutations. This report highlights the need to consider a filaminopathy in the differential diagnosis of craniosynostosis, especially in the presence of atypical cranial or skeletal features.

• 出版日期2015-12